Premium
Sex Differences in Lopinavir and Ritonavir Pharmacokinetics Among HIV‐Infected Women and Men
Author(s) -
Umeh Obi C.,
Currier Judith S.,
Park JeongGun,
Cramer Yoninah,
Hermes Ashwaq E.,
Fletcher Courtney V.
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010388650
Subject(s) - pharmacokinetics , lopinavir , lopinavir/ritonavir , ritonavir , medicine , cmax , pharmacology , human immunodeficiency virus (hiv) , capsule , viral load , virology , antiretroviral therapy , botany , biology
The authors compared the pharmacokinetics of lopinavir (LPV) and ritonavir (RTV) between women and men. This 2‐step, multicenter, pharmacokinetic study enrolled human immunodeficiency virus (HIV)–infected adults on lopinavir/ritonavir (LPV/r) capsules (400/100 mg bid) plus 1 or more nucleoside reverse transcriptase inhibitors. All participants underwent 12‐hour pharmacokinetic sampling. The pharmacokinetic sampling was repeated in participants receiving the LPV/r tablet formulation. Step 1 enrolled 37 women and 40 men; step 2 included 42 participants from step 1 plus 35 new participants (39 women and 38 men). LPV pharmacokinetics in women and men were not significantly different with either formulation. Women had significantly higher median RTV AUC 0–12 h with both the soft‐gel capsule (SGC) and tablet formulations (SGC: 5395 vs 4119 ng·h/mL, P = .026; tablet: 5310 vs 3941 ng·h/mL, P = .012), higher median C max (SGC: 802 vs 635 ng/mL, P = .032; tablet: 773 vs 570 ng/mL, P = .006), and lower median CL/F (SGC: 18.54 vs 24.31 L/h, P = .026; tablet: 18.83 vs 25.37 L/h, P = .012). RTV CL/F was slower in women after weight adjustment with both formulations. The pharmacokinetics of LPV in the SGC and tablet formulations are comparable in HIV‐infected patients. Women had higher RTV AUC 0–12 h and lower CL/F with both formulations. The mechanism of the sex difference in RTV CL/F warrants elucidation.